Diane K. Wherrett
A5068398869- Diabetes and associated disorders
- Diabetes Management and Research
- Pancreatic function and diabetes
- Sexual Differentiation and Disorders
- Immune Cell Function and Interaction
- Urological Disorders and Treatments
- Diabetes Treatment and Management
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- T-cell and B-cell Immunology
- Genomic variations and chromosomal abnormalities
- Thyroid Disorders and Treatments
- Chemokine receptors and signaling
- Immunodeficiency and Autoimmune Disorders
- Urologic and reproductive health conditions
- Neonatal Respiratory Health Research
- Growth Hormone and Insulin-like Growth Factors
- Chromosomal and Genetic Variations
- Neonatal Health and Biochemistry
- Congenital Diaphragmatic Hernia Studies
- Glioma Diagnosis and Treatment
- Hormonal and reproductive studies
- CNS Lymphoma Diagnosis and Treatment
- Genetic Syndromes and Imprinting
- Hair Growth and Disorders
University of Toronto
2016-2025
Hospital for Sick Children
2016-2025
SickKids Foundation
2015-2025
Children's Hospital at Westmead
2023
Palo Alto University
2018
Stanford University
1997-2018
Great Ormond Street Hospital
2009
University College London
2009
Kingston General Hospital
1990
Queen's University
1990
The immunopathogenesis of type 1 diabetes mellitus is associated with T-lymphocyte autoimmunity. However, there growing evidence that B lymphocytes play a role in many T-lymphocyte-mediated diseases. It possible to achieve selective depletion rituximab, an anti-CD20 monoclonal antibody. This phase 2 study evaluated the B-lymphocyte patients diabetes.We conducted randomized, double-blind which 87 between 8 and 40 years age who had newly diagnosed were assigned receive infusions rituximab or...
Type 1 diabetes is a chronic autoimmune disease that leads to destruction of insulin-producing beta cells and dependence on exogenous insulin for survival. Some interventions have delayed the loss production in patients with type diabetes, but might affect clinical progression before diagnosis are needed.We conducted phase 2, randomized, placebo-controlled, double-blind trial teplizumab (an Fc receptor-nonbinding anti-CD3 monoclonal antibody) involving relatives who did not were at high risk...
We previously reported that selective depletion of B-lymphocytes with rituximab, an anti-CD20 monoclonal antibody, slowed decline β-cell function in recent-onset type 1 diabetes mellitus (T1DM) at year. Subjects were followed further to determine whether there was persistence effect.
Teplizumab treatment of nondiabetic relatives at high risk for T1D induces partially exhausted CD8 + T cells and improves beta cell function.
OBJECTIVE Previous studies showed that inhibiting lymphocyte costimulation reduces declining β-cell function in individuals newly diagnosed with type 1 diabetes. We tested whether abatacept would delay or prevent progression of diabetes from normal glucose tolerance (NGT) to abnormal (AGT) and the effects treatment on immune metabolic responses. RESEARCH DESIGN AND METHODS conducted a phase 2, randomized, placebo-controlled, double-masked trial antibody-positive participants NGT who received...
OBJECTIVE We previously reported that 2 years of costimulation modulation with abatacept slowed decline β-cell function in recent-onset type 1 diabetes (T1D). Subsequently, was discontinued and subjects were followed to determine whether there persistence effect. RESEARCH DESIGN AND METHODS Of 112 (ages 6-36 years) T1D, 77 received 35 placebo infusions intravenously for 27 over years. The primary outcome-baseline-adjusted geometric mean 2-h area under the curve (AUC) serum C-peptide during a...
OBJECTIVE A pilot study suggested that combination therapy with low-dose anti-thymocyte globulin (ATG) and pegylated granulocyte colony-stimulating factor (GCSF) preserves C-peptide in established type 1 diabetes (T1D) (duration 4 months to 2 years). We hypothesized 1) ATG/GCSF or 2) ATG alone would slow the decline of β-cell function patients new-onset T1D <100 days). RESEARCH DESIGN AND METHODS three-arm, randomized, double-masked, placebo-controlled trial was performed by Type...
OBJECTIVE We tested the ability of a type 1 diabetes (T1D) genetic risk score (GRS) to predict progression islet autoimmunity and T1D in at-risk individuals. RESEARCH DESIGN AND METHODS studied 1,244 TrialNet Pathway Prevention study participants (T1D patients’ relatives without with one or more positive autoantibodies) who were genotyped Illumina ImmunoChip (median [range] age at initial autoantibody determination 11.1 years [1.2–51.8], 48% male, 80.5% non-Hispanic white, median follow-up...
A three-arm, randomized, double-masked, placebo-controlled phase 2b trial performed by the Type 1 Diabetes TrialNet Study Group previously demonstrated that low-dose anti-thymocyte globulin (ATG) (2.5 mg/kg) preserved β-cell function and reduced HbA1c for year in new-onset type diabetes. Subjects (N = 89) were randomized to 1) ATG pegylated granulocyte colony-stimulating factor (GCSF), 2) alone, or 3) placebo. Herein, we report 2-year area under curve (AUC) C-peptide HbA1c, prespecified...
Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at time stage 3 type 1 diabetes diagnosis, and emerging availability therapy delay disease progression, programmes are being increasingly emphasised. Once broadly implemented, initiatives will identify significant numbers islet autoantibody-positive (IAb
Abstract Differentiation of the bipotential gonad into testis is initiated by Y chromosome‐linked gene SRY (Sex‐determining Region Y) through upregulation its autosomal direct target SOX9 ( Sry ‐related HMG box‐containing 9). Sequence and chromosome homology studies have shown that most probably evolved from SOX3 , which in humans located at Xq27.1. Mutations causing loss‐of‐function do not affect sex determination mice or humans. However, transgenic mouse ectopic expression Sox3 results...
What will it take to bring disease-modifying therapy clinical use in type 1 diabetes? Coordinated efforts of investigators involved discovery, translational, and research operating partnership with funders industry sync regulatory agencies are needed. This Perspective describes one such effort, Type Diabetes TrialNet, a National Institutes Health–funded JDRF-supported international trials network that emerged from the Prevention Trial–Type (DPT-1). Through longitudinal natural history...
Glutamic acid decarboxylase isoform 2 (GAD65; EC 4.1.1.15 ) has been identified as a key target autoantigen of insulin-dependent diabetes mellitus (IDDM). IDDM is genetically associated with the major histocompatibility complex (MHC), and particular alleles from HLA-DQ HLA-DR loci contribute to disease. Among DR4 subtypes, HLA-DRB1*0401, HLA-DRB1*0402, HLA-DRB1*0405 lend susceptibility, while HLA-DRB1*0403 confers protection. We have utilized HLA-DR(α1*0101,β1*0401) (hereafter referred...